Defined three dimensional microenvironment for cell culture

Abstract

Described is a three-dimensional (3D) microenvironment presenting defined biochemical and physical cues that regulate cellular behavior and use of the microenvironment. A composition to form the 3D microenvironment is provided by combining one or more natural or synthetic polymeric materials and substrate proteins recombinantly or chemically functionalized with a variety of bioactive peptides such as extracellular matrix-derived or growth factor-derived peptides. Also described are devices and methods for screening for optimal combinations of the bioactive motifs in order to create an extracellular microenvironment that can regulate specific cellular behavior such as cell growth, proliferation, migration or differentiation.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This application is a continuation-in-part of co-pending U.S. patent application Ser. No. 15 / 173,488, filed Jun. 3, 2016, which itself claims the benefit of the filing date of U.S. Provisional Patent Application Ser. No. 62 / 171,767, filed Jun. 5, 2015, the disclosure of each of which is hereby incorporated herein in its entirety by this reference.TECHNICAL FIELD[0002]This application relates to synthetic microenvironment for culturing cells such as valuable cells including stem cells such as pluripotent stem cells. More particularly, provided are methods and microenvironmental surfaces for culturing pluripotent stem cells, adult stem cells, and adult cells on a defined three-dimensional microenvironment.STATEMENT ACCORDING TO 37 C.F.R. § 1.821(c) or (e)—SEQUENCE LISTING SUBMITTED AS ASCII TEXT FILE[0003]Pursuant to 37 C.F.R. § 1.821(c) or (e), a file containing an ASCII text version of the Sequence Listing has been submitted concomitant wi...

AI Technical Summary

Benefits of technology

The patent describes a 3D microenvironment that can be used to create a cell culture environment that is more like the natural surroundings of cells. This microenvironment can be used to screen different environments for their ability to promote the growth and differentiation of stem cells. The patent also describes the use of specific peptides to activate integrins, which are important proteins involved in cell adhesion and growth. By using this technology, researchers hope to better understand and control the behavior of stem cells in a more accurate way.

Problems solved by technology

These conventional substrates have significant lack of batch-to-batch or lot-to-lot consistency, resulting in experimental variability.

Additionally, current two-dimensional (2D)-based cell culture systems, which suffer from inherent heterogeneity and limited scalability and reproducibility, are emerging as a bottleneck for producing sufficient numbers of high-quality cells for downstream applications.

A major challenge remains with the in vitro expansion and culture of self-renewable stem cells and the subsequent differentiation of these cells.

However, challenges still exist in optimizing the wide variety of platforms capable of supporting cell therapy needs.

However, existing technologies have some limitations to generate a microenvironment that induces a combinatorial signal pathway by selectively, simultaneously or sequentially activating at least two different cell surface receptors in a precisely manner, due to their lack of physical or biochemical attributes.

In addition, various microenvironmental cues are often intertwined and cannot be individually controlled in existing technologies.

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